@article{97e38777f69647379c09ad51017cadec,
title = "Clinical Pharmacogenetics Implementation Consortium Guideline for the Use of Aminoglycosides Based on MT-RNR1 Genotype",
abstract = "Aminoglycosides are widely used antibiotics with notable side effects, such as nephrotoxicity, vestibulotoxicity, and sensorineural hearing loss (cochleotoxicity). MT-RNR1 is a gene that encodes the 12s rRNA subunit and is the mitochondrial homologue of the prokaryotic 16s rRNA. Some MT-RNR1 variants (i.e., m.1095T>C; m.1494C>T; m.1555A>G) more closely resemble the bacterial 16s rRNA subunit and result in increased risk of aminoglycoside-induced hearing loss. Use of aminoglycosides should be avoided in individuals with an MT-RNR1 variant associated with an increased risk of aminoglycoside-induced hearing loss unless the high risk of permanent hearing loss is outweighed by the severity of infection and safe or effective alternative therapies are not available. We summarize evidence from the literature supporting this association and provide therapeutic recommendations for the use of aminoglycosides based on MT-RNR1 genotype (updates at https://cpicpgx.org/guidelines/ and www.pharmgkb.org).",
author = "McDermott, {John Henry} and Joshua Wolf and Keito Hoshitsuki and Rachel Huddart and Caudle, {Kelly E.} and Michelle Whirl-Carrillo and Steyger, {Peter S.} and Smith, {Richard J.H.} and Neal Cody and Cristina Rodriguez-Antona and Klein, {Teri E.} and Newman, {William G.}",
note = "Funding Information: This work was funded by the National Institutes of Health (NIH) for CPIC (K.E.C. and T.E.K. U24HG010135) and PharmGKB (R.H., T.E.K., and M.W.‐C., U24HG010615). K.H. is supported by the National Institutes of Health grant TL1TR001858 and the Rho Chi Society and American Foundation for Pharmaceutical Education. W.G.N. is supported by the Manchester NIHR BRC (IS‐BRC‐1215‐20007). P.S.S. is supported by NIDCD R01s: DC004555 and DC016680. RJHS is supported by NIDCD R01s: DC002842, DC012049, and DC017955. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health (NIH). Funding Information: This work was funded by the National Institutes of Health (NIH) for CPIC (K.E.C. and T.E.K. U24HG010135) and PharmGKB (R.H., T.E.K., and M.W.-C., U24HG010615). K.H. is supported by the National Institutes of Health grant TL1TR001858 and the Rho Chi Society and American Foundation for Pharmaceutical Education. W.G.N. is supported by the Manchester NIHR BRC (IS-BRC-1215-20007). P.S.S. is supported by NIDCD R01s: DC004555 and DC016680. RJHS is supported by NIDCD R01s: DC002842, DC012049, and DC017955. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health (NIH). The authors acknowledge the critical input of Dr. Mary V. Relling (St. Jude Children?s Research Hospital) and the members of the Clinical Pharmacogenetics Implementation Consortium (CPIC). Publisher Copyright: {\textcopyright} 2021 The Authors. Clinical Pharmacology & Therapeutics {\textcopyright} 2021 American Society for Clinical Pharmacology and Therapeutics",
year = "2022",
month = feb,
doi = "10.1002/cpt.2309",
language = "English (US)",
volume = "111",
pages = "366--372",
journal = "Clinical Pharmacology and Therapeutics",
issn = "0009-9236",
publisher = "Nature Publishing Group",
number = "2",
}